Opioid action was thought to exert reinforcing effects solely via the initial agonism of opioid receptors. Here, we present evidence for an additional novel contributor to opioid reward: the innate ...immune pattern-recognition receptor, toll-like receptor 4 (TLR4), and its MyD88-dependent signaling. Blockade of TLR4/MD2 by administration of the nonopioid, unnatural isomer of naloxone, (+)-naloxone (rats), or two independent genetic knock-outs of MyD88-TLR4-dependent signaling (mice), suppressed opioid-induced conditioned place preference. (+)-Naloxone also reduced opioid (remifentanil) self-administration (rats), another commonly used behavioral measure of drug reward. Moreover, pharmacological blockade of morphine-TLR4/MD2 activity potently reduced morphine-induced elevations of extracellular dopamine in rat nucleus accumbens, a region critical for opioid reinforcement. Importantly, opioid-TLR4 actions are not a unidirectional influence on opioid pharmacodynamics, since TLR4(-/-) mice had reduced oxycodone-induced p38 and JNK phosphorylation, while displaying potentiated analgesia. Similar to our recent reports of morphine-TLR4/MD2 binding, here we provide a combination of in silico and biophysical data to support (+)-naloxone and remifentanil binding to TLR4/MD2. Collectively, these data indicate that the actions of opioids at classical opioid receptors, together with their newly identified TLR4/MD2 actions, affect the mesolimbic dopamine system that amplifies opioid-induced elevations in extracellular dopamine levels, therefore possibly explaining altered opioid reward behaviors. Thus, the discovery of TLR4/MD2 recognition of opioids as foreign xenobiotic substances adds to the existing hypothesized neuronal reinforcement mechanisms, identifies a new drug target in TLR4/MD2 for the treatment of addictions, and provides further evidence supporting a role for central proinflammatory immune signaling in drug reward.
There is little appreciation of the level of extinction risk faced by one‐sixth of the over 65,000 species assessed by the International Union for Conservation of Nature. Determining the status of ...these data‐deficient (DD) species is essential to developing an accurate picture of global biodiversity and identifying potentially threatened DD species. To address this knowledge gap, we used predictive models incorporating species’ life history, geography, and threat information to predict the conservation status of DD terrestrial mammals. We constructed the models with 7 machine learning (ML) tools trained on species of known status. The resultant models showed very high species classification accuracy (up to 92%) and ability to correctly identify centers of threatened species richness. Applying the best model to DD species, we predicted 313 of 493 DD species (64%) to be at risk of extinction, which increases the estimated proportion of threatened terrestrial mammals from 22% to 27%. Regions predicted to contain large numbers of threatened DD species are already conservation priorities, but species in these areas show considerably higher levels of risk than previously recognized. We conclude that unless directly targeted for monitoring, species classified as DD are likely to go extinct without notice. Taking into account information on DD species may therefore help alleviate data gaps in biodiversity indicators and conserve poorly known biodiversity.
Cryovolcanism on Ceres Ruesch, O.; Platz, T.; Schenk, P. ...
Science (American Association for the Advancement of Science),
09/2016, Letnik:
353, Številka:
6303
Journal Article
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Odprti dostop
Volcanic edifices are abundant on rocky bodies of the inner solar system. In the cold outer solar system, volcanism can occur on solid bodies with a water-ice shell, but derived cryovolcanic ...constructs have proved elusive. We report the discovery, using Dawn Framing Camera images, of a landform on dwarf planet Ceres that we argue represents a viscous cryovolcanic dome. Parent material of the cryomagma is a mixture of secondary minerals, including salts and water ice. Absolute model ages from impact craters reveal that extrusion of the dome has occurred recently. Ceres' evolution must have been able to sustain recent interior activity and associated surface expressions. We propose salts with low eutectic temperatures and thermal conductivities as key drivers for Ceres' long-term internal evolution.
Since echinocandins are recommended as first line therapy for invasive candidiasis, detection of resistance, mainly due to alteration in FKS protein, is of main interest. EUCAST AFST recommends ...testing both MIC of anidulafungin and micafungin, and breakpoints (BPs) have been proposed to detect echinocandin-resistant isolates. We analyzed MIC distribution for all three available echinocandins of 2,787 clinical yeast isolates corresponding to 5 common and 16 rare yeast species, using the standardized EUCAST method for anidulafungin and modified for caspofungin and micafungin (AM3-MIC). In our database, 64 isolates of common pathogenic species were resistant to anidulafungin, according to the EUCAST BP, and/or to caspofungin, using our previously published threshold (AM3-MIC ≥ 0.5 mg/L). Among these 64 isolates, 50 exhibited 21 different FKS mutations. We analyzed the capacity of caspofungin AM3-MIC and anidulafungin MIC determination in detecting isolates with FKS mutation. They were always identified using caspofungin AM3-MIC and the local threshold while some isolates were misclassified using anidulafungin MIC and EUCAST threshold. However, both methods misclassified four wild-type C. glabrata as resistant. Based on a large data set from a single center, the use of AM3-MIC testing for caspofungin looks promising in identifying non-wild-type C. albicans, C. tropicalis and P. kudiravzevii isolates, but additional multicenter comparison is mandatory to conclude on the possible superiority of AM3-MIC testing compared to the EUCAST method.
ABSTRACT
We present the results from an analysis of deep Herschel far-infrared (far-IR) observations of the edge-on disc galaxy NGC 3079. The point spread function-cleaned Photodetector Array Camera ...and Spectrometer (PACS) images at 100 and 160 µm display a 25 × 25 kpc2 X-shape structure centred on the nucleus that is similar in extent and orientation to that seen in H α, X-rays, and the far-ultraviolet. One of the dusty filaments making up this structure is detected in the Spectral and Photometric Imaging Receiver 250 µm map out to ∼25 kpc from the nucleus. The match between the far-IR filaments and those detected at other wavelengths suggests that the dusty material has been lifted out of the disc by the same large-scale galactic wind that has produced the other structures in this object. A closer look at the central 10 × 10 kpc2 region provides additional support for this scenario. The dust temperatures traced by the 100–160 µm flux ratios in this region are enhanced within a biconical region centred on the active galactic nucleus, aligned along the minor axis of the galaxy, and coincident with the well-known double-lobed cm-wave radio structure and H α–X-ray nuclear superbubbles. PACS imaging spectroscopy of the inner 6 kpc region reveals broad C ii 158 µm emission line profiles and OH 79 µm absorption features along the minor axis of the galaxy with widths well in excess of those expected from beam smearing of the disc rotational motion. This provides compelling evidence that the cool material traced by the C ii and OH features directly interacts with the nuclear ionized and relativistic outflows traced by the H α, X-ray, and radio emission.
We present a comprehensive global catalog of the geomorphological features with clear or potential relevance to subsurface ice identified during the Dawn spacecraft's primary and first extended ...missions at Ceres. We define eight broad feature classes and describe analyses supporting their genetic links to subsurface ice. These classes include relaxed craters; central pit craters; large domes; small mounds; lobate landslides and ejecta; pitted materials; depressions and scarps; and fractures, grooves, and channels. Features in all classes are widely distributed on the dwarf planet, consistent with multiple lines of observational evidence that ice is a key component of Ceres' crust. Independent analyses of multiple feature types suggest rheological and compositional layering may be common in the upper ~10 km of the crust. Clustering of features indicates that ice concentration is heterogeneous on nearly all length scales, from ~1 km to hundreds of kilometers. Impacts are likely the key driver of heterogeneity, causing progressive devolatilization of the low latitude and midlatitude crust on billion‐year timescales but also producing localized enhancements in near surface ice content via excavation of deep ice‐rich material and possible facilitation of cryomagmatic and cryovolcanic activity. Impacts and landslides may be the dominant mechanism for ice loss on modern Ceres. Our analysis suggests specific locations where future high‐resolution imaging can be used to probe (1) current volatile loss rates and (2) the history of putative cryomagmatic and cryovolcanic features. The Cerean cryosphere and its unique morphology promise to be a rich subject of ongoing research for years to come.
Plain language summary
Planetary scientists are interested in understanding where ice is located in the solar system for two reasons. First, water is necessary to sustain life as we know it, so extraterrestrial ice may provide habitats for past or present life. Second, water ice can be used to produce rocket fuel; in the future, ice may be mined from asteroids, moons, and planets to fuel spacecraft carrying humans. Ceres has been predicted to contain large amounts of ice for decades. When the Dawn spacecraft arrived at Ceres, a major goal for the science team was confirming the presence of ice and understanding how it is distributed beneath the surface. One aspect of that investigation was identifying landforms (features like mountains or craters on the surface) whose appearance indicates the presence of ice. In this study, we compiled a catalog and global maps of all of the “icy” landforms identified during Dawn's primary mission at Ceres. We used these maps, together with detailed analysis of each type of landform, to develop a global picture of how ice is distributed in Ceres' crust. We found that the concentration of ice was spatially variable and that layering of icy and less icy materials may be common. We also identified specific areas of Ceres that may be particularly ice‐rich, so that future missions can target these areas for more analysis.
Key Points
We present a global catalog and maps of the morphological features relevant to subsurface ice identified during the Dawn mission at Ceres
Morphology suggests ice concentration is heterogeneous in the upper kilometers of Ceres' crust; impacts likely contribute to heterogeneity
We highlight locations where future analysis may provide insights into putative cryovolcanic features and current H2O loss mechanisms
The corrosion behavior for several die-cast Mg-Al alloys (AM50, AM50, and AZ91) was compared to commercial purity Mg and AZ31B-H24 utilizing simultaneous measurement of electrochemical impedance ...spectroscopy (EIS), hydrogen gas collection over a 24 h immersion period, gravimetric mass loss, and inductively coupled plasma optical emission spectrometry (ICP-OES) solution analysis of the total Mg concentration released. Tests were conducted in three electrolytes, unbuffered 0.6 M NaCl, 0.1 M tris(hydroxymethyl)aminomethane (TRIS), and 0.6 M NaCl buffered with TRIS to a pH of 7. EIS derived polarization resistance was monitored periodically, as determined from EIS circuit modeling using data collected to 0.001 Hz, and considering the pseudo-inductive low-frequency impedance time constant. EIS derived corrosion rates and oxidation charge density were similar to charge density determined from cumulative mass loss, ICP-OES solution analysis, and the volume of hydrogen collected for the die-cast AM50, AM60, and AZ91, as well as for Mg and AZ31B determined previously. The variation in the cathodic hydrogen evolution reaction kinetics for the die-cast alloys were also determined over 0, 3, 12, and 24 h immersion periods and compared to commercial purity Mg and AZ31B-H24. The global corrosion rate decreased with increasing Al content, even though Al wt% above the solubility limit (2 wt% at room temperature) resulted in increasing volume fractions of the Al8Mn5(Fe), Al2Mn3, and Al3Fe intermetallic particles. Each of the alloys contained varying volume fractions of primary α, β-phase (Mg17Al12), and eutectic α+β depending on Al content and processing. Al in the solid solution α-Mg phase decreased the overall net anodic reaction rate for the Mg2+ half-cell reaction. The Mg17Al12 phase was reasoned to not function as a strong cathode as deduced from cathodic E-log(i) studies. Moreover, the extent of anodically-induced cathodic activation was speculated to decrease with increasing Al content, which was a factor in determining overall corrosion rate and accumulated damage. However, corrosion damage depth as determined from a pitting factor analysis increased with Al content.
Exposure to green space and nature has a potential role to play in the care of people with dementia, with possible benefits including improved mood and slower disease progression. In this ...observational study at a dementia care facility in the UK, we used carer-assessed measures to evaluate change in mood of residents with mid- to late-stage dementia following exposure to a nature garden. We found that exposure to nature was associated with a beneficial change in patient mood. There was a non-linear relationship between time spent outdoors and mood outcome. Improvements in patient mood were associated with relatively short duration exposures to nature, and no additional measureable increases in mood were found with exposures beyond 80–90 minutes duration. Whilst further investigation is required before causality can be determined, these results raise important questions for policy about the integration of outdoor space into the design of dementia care facilities and programmes.
One in 6 species (13,465 species) on the International Union for Conservation of Nature (IUCN) Red List is classified as data deficient due to lack of information on their taxonomy, population ...status, or impact of threats. Despite the chance that many are at high risk of extinction, data-deficient species are typically excluded from global and local conservation priorities, as well as funding schemes. The number of data-deficient species will greatly increase as the IUCN Red List becomes more inclusive of poorly known and speciose groups. A strategic approach is urgently needed to enhance the conservation value of data-deficient assessments. To develop this, we reviewed 2879 data-deficient assessments in 6 animal groups and identified 8 main justifications for assigning data-deficient status (type series, few records, old records, uncertain provenance, uncertain population status or distribution, uncertain threats, taxonomic uncertainty, and new species). Assigning a consistent set of justification tags (i.e., consistent assignment to assessment justifications) to species classified as data deficient is a simple way to achieve more strategic assessments. Such tags would clarify the causes of data deficiency; facilitate the prediction of extinction risk; facilitate comparisons of data deficiency among taxonomic groups; and help prioritize species for reassessment. With renewed efforts, it could be straightforward to prevent thousands of data-deficient species slipping unnoticed toward extinction. Una de cada seis especies (13,465 especies) en la Lista Roja de la Unión Internacional para la Conservación de la Naturaleza (UICN) está clasificada como con datos deficientes debido a la carencia de información sobre su taxonomía, el estado de la población o el impacto de las amenazas. A pesar de la probabilidad de que muchas tengan un alto riesgo de extinción, las especies con datos deficientes típicamente son excluidas de las prioridades globales y locales de conservación, así como de los esquemas de financiamiento. El número de especies con datos deficientes incrementará enormemente conforme la Lista Roja de la UICN se vuelva más incluyente con los grupos con especies numerosas y poco conocidas. Se requiere urgentemente un enfoque estratégico para aumentar el valor de conservación de las evaluaciones con datos deficeintes. Para desarrollar esto, revisamos 2, 879 evaluaciones con datos deficeintes en seis grupos animales e identificamos ocho justificaciones principales para la designación del estado datos deficientes (serie tipo, pocos registros, registros viejos, procedencia incierta, estado de población o distribución incierta, amenazas inciertas, incertidumbre taxonómica, especies nuevas). Designar un conjunto consistente de etiquetas de justificación (es decir, designación consistente a las justificaciones evaluadas) a las especies clasificadas como con datos deficientes es una manera simple de obtener evaluaciones más estratégicas. Dichas etiquetas clarificarían las causas de la deficiencia de datos; facilitarían la predicción del riesgo de extinción; facilitarían las comparaciones de la deficiencia de datos entre los grupos taxonómicos; y ayudarían a priorizar especies para su re-evaluación. Con esfuerzos renovados, podría ser más sencillo prevenir que miles de especies con datos deficientes pasen desapercibidas hacia la extinción.
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